Effectiveness and Safety of Non–vitamin K Antagonist Oral Anticoagulants for Atrial Fibrillation and Venous Thromboembolism: A Systematic Review and Meta-analyses

Abdulaali R. Almutairi, Lili Zhou, Walid F. Gellad, Jeannie K Lee, Marion K Slack, Jennifer R. Martin, Wei Hsuan Lo-Ciganic

Research output: Contribution to journalReview article

31 Citations (Scopus)

Abstract

Purpose The findings from the observational studies comparing the effectiveness and safety of non–vitamin K antagonist oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) for atrial fibrillation (AF) and venous thromboembolism (VTE) are inconsistent. We conducted separate meta-analyses examining the efficacy/effectiveness and safety of NOACs versus VKAs by disease (AF vs VTE), study design (randomized controlled trials [RCTs] vs observational studies), and NOAC (dabigatran, rivaroxaban, apixaban, and edoxaban). Methods The main data sources included PubMed/MEDLINE, EMBASE, Web of Science, CINAHL, and Scopus from January 1, 2005, to February 15, 2016. We searched for Phase III RCTs and observational studies comparing NOACs versus VKAs. The primary outcomes were stroke/systemic embolism (SE) for AF; recurrent VTE/fatal pulmonary embolism (PE) for VTE; and major bleeding for both conditions. Secondary outcomes included stroke and myocardial infarction (MI) for AF, recurrent deep vein thrombosis (DVT)/PE for VTE, and mortality, intracranial hemorrhage (ICH), and gastrointestinal bleeding for both conditions. Pooled hazard ratios (HRs) were reported by using inverse variance–weighted random effects models. Findings A total of 13 RCTs and 27 observational studies (AF, n = 32; VTE, n = 8) were included. For AF, dabigatran and VKAs were comparable for stroke/SE risk in 1 RCT (HR, 0.77 [95% CI, 0.57–1.03]) and 6 observational studies (HR, 1.03 [95% CI, 0.83–1.27]). Rivaroxaban had a 20% decreased risk of stroke/SE in 3 RCTs (HR, 0.80 [95% CI, 0.67–0.95]) compared with VKA, but the effect was nonsignificant in 3 observational studies (HR, 0.78 [95% CI, 0.59–1.04]). Apixaban decreased stroke/systemic embolism risk (HR, 0.79 [95% CI, 0.66–0.95]) compared with VKA in 1 RCT, but edoxaban was comparable to VKA (HR, 0.99 [95% CI, 0.77–1.28]) in 1 RCT (no observational studies available for apixaban/edoxaban). Dabigatran, apixaban, and edoxaban decreased the risk of hemorrhagic stroke, mortality, major bleeding, and ICH by 10% to 71% compared with VKAs but not rivaroxaban. For VTE, NOACs and VKAs were comparable for recurrent VTE/fatal PE/DVT/PE risk in 7 RCTs and 1 observational study. The 7 RCTs demonstrated a 32% to 69% decreased risk of major bleeding for dabigatran, rivaroxaban, and apixaban compared with VKAs. No difference was shown in 1 rivaroxaban observational study (HR, 0.77 [95% CI, 0.40–1.49]) and 1 edoxaban RCT (HR, 0.84 [95% CI, 0.59–1.20]). Except for dabigatran, the NOACs had a 61% to 86% decreased risk of ICH and gastrointestinal bleeding. Implications Overall, NOACs were comparable or superior to VKAs. Although no observational studies are currently available for apixaban/edoxaban, a few notable inconsistencies exist for dabigatran (ischemic stroke, MI) and rivaroxaban (stroke/SE, major bleeding in VTE) between RCTs and observational studies. Individualizing NOAC/VKA therapy based on benefit/safety profiles and patient characteristics is suggested.

Original languageEnglish (US)
Pages (from-to)1456-1478.e36
JournalClinical Therapeutics
Volume39
Issue number7
DOIs
StatePublished - Jul 1 2017

Fingerprint

Vitamin K
Venous Thromboembolism
Anticoagulants
Atrial Fibrillation
Meta-Analysis
Observational Studies
Randomized Controlled Trials
Safety
Stroke
Embolism
Hemorrhage
Pulmonary Embolism
Intracranial Hemorrhages
Venous Thrombosis
Myocardial Infarction
Mortality
Information Storage and Retrieval
Patient Safety
PubMed
MEDLINE

Keywords

  • atrial fibrillation
  • bleeding
  • meta-analysis
  • non–vitamin K antagonist oral anticoagulants
  • venous thromboembolism
  • warfarin

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Effectiveness and Safety of Non–vitamin K Antagonist Oral Anticoagulants for Atrial Fibrillation and Venous Thromboembolism : A Systematic Review and Meta-analyses. / Almutairi, Abdulaali R.; Zhou, Lili; Gellad, Walid F.; Lee, Jeannie K; Slack, Marion K; Martin, Jennifer R.; Lo-Ciganic, Wei Hsuan.

In: Clinical Therapeutics, Vol. 39, No. 7, 01.07.2017, p. 1456-1478.e36.

Research output: Contribution to journalReview article

Almutairi, Abdulaali R. ; Zhou, Lili ; Gellad, Walid F. ; Lee, Jeannie K ; Slack, Marion K ; Martin, Jennifer R. ; Lo-Ciganic, Wei Hsuan. / Effectiveness and Safety of Non–vitamin K Antagonist Oral Anticoagulants for Atrial Fibrillation and Venous Thromboembolism : A Systematic Review and Meta-analyses. In: Clinical Therapeutics. 2017 ; Vol. 39, No. 7. pp. 1456-1478.e36.
@article{f5d642aad39c4a6f8fdfe665fac584a9,
title = "Effectiveness and Safety of Non–vitamin K Antagonist Oral Anticoagulants for Atrial Fibrillation and Venous Thromboembolism: A Systematic Review and Meta-analyses",
abstract = "Purpose The findings from the observational studies comparing the effectiveness and safety of non–vitamin K antagonist oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) for atrial fibrillation (AF) and venous thromboembolism (VTE) are inconsistent. We conducted separate meta-analyses examining the efficacy/effectiveness and safety of NOACs versus VKAs by disease (AF vs VTE), study design (randomized controlled trials [RCTs] vs observational studies), and NOAC (dabigatran, rivaroxaban, apixaban, and edoxaban). Methods The main data sources included PubMed/MEDLINE, EMBASE, Web of Science, CINAHL, and Scopus from January 1, 2005, to February 15, 2016. We searched for Phase III RCTs and observational studies comparing NOACs versus VKAs. The primary outcomes were stroke/systemic embolism (SE) for AF; recurrent VTE/fatal pulmonary embolism (PE) for VTE; and major bleeding for both conditions. Secondary outcomes included stroke and myocardial infarction (MI) for AF, recurrent deep vein thrombosis (DVT)/PE for VTE, and mortality, intracranial hemorrhage (ICH), and gastrointestinal bleeding for both conditions. Pooled hazard ratios (HRs) were reported by using inverse variance–weighted random effects models. Findings A total of 13 RCTs and 27 observational studies (AF, n = 32; VTE, n = 8) were included. For AF, dabigatran and VKAs were comparable for stroke/SE risk in 1 RCT (HR, 0.77 [95{\%} CI, 0.57–1.03]) and 6 observational studies (HR, 1.03 [95{\%} CI, 0.83–1.27]). Rivaroxaban had a 20{\%} decreased risk of stroke/SE in 3 RCTs (HR, 0.80 [95{\%} CI, 0.67–0.95]) compared with VKA, but the effect was nonsignificant in 3 observational studies (HR, 0.78 [95{\%} CI, 0.59–1.04]). Apixaban decreased stroke/systemic embolism risk (HR, 0.79 [95{\%} CI, 0.66–0.95]) compared with VKA in 1 RCT, but edoxaban was comparable to VKA (HR, 0.99 [95{\%} CI, 0.77–1.28]) in 1 RCT (no observational studies available for apixaban/edoxaban). Dabigatran, apixaban, and edoxaban decreased the risk of hemorrhagic stroke, mortality, major bleeding, and ICH by 10{\%} to 71{\%} compared with VKAs but not rivaroxaban. For VTE, NOACs and VKAs were comparable for recurrent VTE/fatal PE/DVT/PE risk in 7 RCTs and 1 observational study. The 7 RCTs demonstrated a 32{\%} to 69{\%} decreased risk of major bleeding for dabigatran, rivaroxaban, and apixaban compared with VKAs. No difference was shown in 1 rivaroxaban observational study (HR, 0.77 [95{\%} CI, 0.40–1.49]) and 1 edoxaban RCT (HR, 0.84 [95{\%} CI, 0.59–1.20]). Except for dabigatran, the NOACs had a 61{\%} to 86{\%} decreased risk of ICH and gastrointestinal bleeding. Implications Overall, NOACs were comparable or superior to VKAs. Although no observational studies are currently available for apixaban/edoxaban, a few notable inconsistencies exist for dabigatran (ischemic stroke, MI) and rivaroxaban (stroke/SE, major bleeding in VTE) between RCTs and observational studies. Individualizing NOAC/VKA therapy based on benefit/safety profiles and patient characteristics is suggested.",
keywords = "atrial fibrillation, bleeding, meta-analysis, non–vitamin K antagonist oral anticoagulants, venous thromboembolism, warfarin",
author = "Almutairi, {Abdulaali R.} and Lili Zhou and Gellad, {Walid F.} and Lee, {Jeannie K} and Slack, {Marion K} and Martin, {Jennifer R.} and Lo-Ciganic, {Wei Hsuan}",
year = "2017",
month = "7",
day = "1",
doi = "10.1016/j.clinthera.2017.05.358",
language = "English (US)",
volume = "39",
pages = "1456--1478.e36",
journal = "Clinical Therapeutics",
issn = "0149-2918",
publisher = "Excerpta Medica",
number = "7",

}

TY - JOUR

T1 - Effectiveness and Safety of Non–vitamin K Antagonist Oral Anticoagulants for Atrial Fibrillation and Venous Thromboembolism

T2 - A Systematic Review and Meta-analyses

AU - Almutairi, Abdulaali R.

AU - Zhou, Lili

AU - Gellad, Walid F.

AU - Lee, Jeannie K

AU - Slack, Marion K

AU - Martin, Jennifer R.

AU - Lo-Ciganic, Wei Hsuan

PY - 2017/7/1

Y1 - 2017/7/1

N2 - Purpose The findings from the observational studies comparing the effectiveness and safety of non–vitamin K antagonist oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) for atrial fibrillation (AF) and venous thromboembolism (VTE) are inconsistent. We conducted separate meta-analyses examining the efficacy/effectiveness and safety of NOACs versus VKAs by disease (AF vs VTE), study design (randomized controlled trials [RCTs] vs observational studies), and NOAC (dabigatran, rivaroxaban, apixaban, and edoxaban). Methods The main data sources included PubMed/MEDLINE, EMBASE, Web of Science, CINAHL, and Scopus from January 1, 2005, to February 15, 2016. We searched for Phase III RCTs and observational studies comparing NOACs versus VKAs. The primary outcomes were stroke/systemic embolism (SE) for AF; recurrent VTE/fatal pulmonary embolism (PE) for VTE; and major bleeding for both conditions. Secondary outcomes included stroke and myocardial infarction (MI) for AF, recurrent deep vein thrombosis (DVT)/PE for VTE, and mortality, intracranial hemorrhage (ICH), and gastrointestinal bleeding for both conditions. Pooled hazard ratios (HRs) were reported by using inverse variance–weighted random effects models. Findings A total of 13 RCTs and 27 observational studies (AF, n = 32; VTE, n = 8) were included. For AF, dabigatran and VKAs were comparable for stroke/SE risk in 1 RCT (HR, 0.77 [95% CI, 0.57–1.03]) and 6 observational studies (HR, 1.03 [95% CI, 0.83–1.27]). Rivaroxaban had a 20% decreased risk of stroke/SE in 3 RCTs (HR, 0.80 [95% CI, 0.67–0.95]) compared with VKA, but the effect was nonsignificant in 3 observational studies (HR, 0.78 [95% CI, 0.59–1.04]). Apixaban decreased stroke/systemic embolism risk (HR, 0.79 [95% CI, 0.66–0.95]) compared with VKA in 1 RCT, but edoxaban was comparable to VKA (HR, 0.99 [95% CI, 0.77–1.28]) in 1 RCT (no observational studies available for apixaban/edoxaban). Dabigatran, apixaban, and edoxaban decreased the risk of hemorrhagic stroke, mortality, major bleeding, and ICH by 10% to 71% compared with VKAs but not rivaroxaban. For VTE, NOACs and VKAs were comparable for recurrent VTE/fatal PE/DVT/PE risk in 7 RCTs and 1 observational study. The 7 RCTs demonstrated a 32% to 69% decreased risk of major bleeding for dabigatran, rivaroxaban, and apixaban compared with VKAs. No difference was shown in 1 rivaroxaban observational study (HR, 0.77 [95% CI, 0.40–1.49]) and 1 edoxaban RCT (HR, 0.84 [95% CI, 0.59–1.20]). Except for dabigatran, the NOACs had a 61% to 86% decreased risk of ICH and gastrointestinal bleeding. Implications Overall, NOACs were comparable or superior to VKAs. Although no observational studies are currently available for apixaban/edoxaban, a few notable inconsistencies exist for dabigatran (ischemic stroke, MI) and rivaroxaban (stroke/SE, major bleeding in VTE) between RCTs and observational studies. Individualizing NOAC/VKA therapy based on benefit/safety profiles and patient characteristics is suggested.

AB - Purpose The findings from the observational studies comparing the effectiveness and safety of non–vitamin K antagonist oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) for atrial fibrillation (AF) and venous thromboembolism (VTE) are inconsistent. We conducted separate meta-analyses examining the efficacy/effectiveness and safety of NOACs versus VKAs by disease (AF vs VTE), study design (randomized controlled trials [RCTs] vs observational studies), and NOAC (dabigatran, rivaroxaban, apixaban, and edoxaban). Methods The main data sources included PubMed/MEDLINE, EMBASE, Web of Science, CINAHL, and Scopus from January 1, 2005, to February 15, 2016. We searched for Phase III RCTs and observational studies comparing NOACs versus VKAs. The primary outcomes were stroke/systemic embolism (SE) for AF; recurrent VTE/fatal pulmonary embolism (PE) for VTE; and major bleeding for both conditions. Secondary outcomes included stroke and myocardial infarction (MI) for AF, recurrent deep vein thrombosis (DVT)/PE for VTE, and mortality, intracranial hemorrhage (ICH), and gastrointestinal bleeding for both conditions. Pooled hazard ratios (HRs) were reported by using inverse variance–weighted random effects models. Findings A total of 13 RCTs and 27 observational studies (AF, n = 32; VTE, n = 8) were included. For AF, dabigatran and VKAs were comparable for stroke/SE risk in 1 RCT (HR, 0.77 [95% CI, 0.57–1.03]) and 6 observational studies (HR, 1.03 [95% CI, 0.83–1.27]). Rivaroxaban had a 20% decreased risk of stroke/SE in 3 RCTs (HR, 0.80 [95% CI, 0.67–0.95]) compared with VKA, but the effect was nonsignificant in 3 observational studies (HR, 0.78 [95% CI, 0.59–1.04]). Apixaban decreased stroke/systemic embolism risk (HR, 0.79 [95% CI, 0.66–0.95]) compared with VKA in 1 RCT, but edoxaban was comparable to VKA (HR, 0.99 [95% CI, 0.77–1.28]) in 1 RCT (no observational studies available for apixaban/edoxaban). Dabigatran, apixaban, and edoxaban decreased the risk of hemorrhagic stroke, mortality, major bleeding, and ICH by 10% to 71% compared with VKAs but not rivaroxaban. For VTE, NOACs and VKAs were comparable for recurrent VTE/fatal PE/DVT/PE risk in 7 RCTs and 1 observational study. The 7 RCTs demonstrated a 32% to 69% decreased risk of major bleeding for dabigatran, rivaroxaban, and apixaban compared with VKAs. No difference was shown in 1 rivaroxaban observational study (HR, 0.77 [95% CI, 0.40–1.49]) and 1 edoxaban RCT (HR, 0.84 [95% CI, 0.59–1.20]). Except for dabigatran, the NOACs had a 61% to 86% decreased risk of ICH and gastrointestinal bleeding. Implications Overall, NOACs were comparable or superior to VKAs. Although no observational studies are currently available for apixaban/edoxaban, a few notable inconsistencies exist for dabigatran (ischemic stroke, MI) and rivaroxaban (stroke/SE, major bleeding in VTE) between RCTs and observational studies. Individualizing NOAC/VKA therapy based on benefit/safety profiles and patient characteristics is suggested.

KW - atrial fibrillation

KW - bleeding

KW - meta-analysis

KW - non–vitamin K antagonist oral anticoagulants

KW - venous thromboembolism

KW - warfarin

UR - http://www.scopus.com/inward/record.url?scp=85021285696&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85021285696&partnerID=8YFLogxK

U2 - 10.1016/j.clinthera.2017.05.358

DO - 10.1016/j.clinthera.2017.05.358

M3 - Review article

C2 - 28668628

AN - SCOPUS:85021285696

VL - 39

SP - 1456-1478.e36

JO - Clinical Therapeutics

JF - Clinical Therapeutics

SN - 0149-2918

IS - 7

ER -